As mankind has developed into a rich society, obesity has become one of the most serious diseases, and thus the World Health Organization (WHO) has declared that obesity is a target of diseases to be treated. Obesity is a metabolic disorder caused by an imbalance between intake and consumption of calories, and is caused by hypertrophy or hyperplasia of adipocytes in the body morphologically. Obesity is not only the most common malnutrition disorder in western society, but also in Korea, the importance of the treatment and prevention of obesity is rapidly increasing due to the rapid increase in the frequency of obesity due to the improvement of diet and westernization of lifestyle, which result from economic advances. Obesity is an important factor that not only psychologically disturbs individuals, but also increases the risk of various adult diseases socially. Obesity is known to be directly associated with the increased prevalence of various adult diseases such as type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, and the like (Cell 87:377, 1999), all obesity-associated diseases are referred to as metabolic syndrome or insulin resistance syndrome, and these have been found as causes of arteriosclerosis and cardiovascular diseases. From the fact that obesity increases the incidence rate of various metabolic diseases and actual weight loss significantly reduces the incidence rate of such diseases, it can be inferred that fat-rich adipocytes mediate this phenomenon.
In the past, adipose tissue was considered to be an energy storage organ that stores excessive energy in the form of a triacylglycerol and releases it when needed, but has recently been accepted as an important endocrine organ that regulates energy homeostasis by secreting various adipokines, such as adiponectin, leptin, resistin, and the like (Trends Endocrinol Metab 13:18, 2002). Therefore, understanding of the proliferation of adipocytes and substances secreted by adipocytes and verification of their in vivo regulatory mechanisms are considered to serve as a basis for understanding obesity and various diseases caused thereby and for developing an effective therapeutic agent, and accordingly, studies on the regulation of adipocyte differentiation have been actively conducted, and it is considered to be the main mechanism that an increased number of adipocytes in patients with obesity originates from differentiation from pre-adipocytes in the body. Research on the differentiation process of pre-adipocytes into adipocytes has been conducted using cells such as 3T3-L1, and various types of transcription factors, particularly transcription factors known to be involved in adipogenesis, CAAT enhancer binding proteins (C/EBPs), peroxisome proliferator activated receptors (PPARs), and adipocyte determination and differentiation dependent factor1/sterol response element binding proteins (ADD1/SREBPs) are known to be expressed according to time differences and regulate the process (Bart A Jessen et al., Gene, 299, pp 95-100, 2002; Darlington et al., J. Biol. Chem., 273, pp 30057-30060, 1998; Brun R. P et al., Curr. Opin. Cell. Biol., 8, pp 826-832, 1996). Upon stimulation of hormones such as isobutylmethylxanthin, dexamethasone and insulin (MDI), C/EBPβ and C/EBPδ are first transiently expressed and initiates differentiation into adipocytes (Reusch J. E et al., Mol. Cell. Biol., 20, pp 1008-1020, 2000). This in turn induces increased expression of C/EBPδ and PPARg (James M. N. et al., J. Nutr., 130, pp 3122S-3126S, 2000). PPARg is known to be an especially important transcription factor for adipocyte differentiation, forms a dimer with a retinoic acid X receptor protein, and then binds to peroxisome proliferator response elements (PPREs) present in the promoters of various adipocyte genes (Tontonoz P. E et al., Genes Dev., 8, pp 1224-1234, 1994; Hwang, C. S et al., Cell Dev. Biol., 13, pp 873-877). The interaction of PPARγ and C/EBP-α is very crucial for differentiation into mature adipocytes, these transcription factors and adipocyte regulators stimulate differentiation into adipocytes, and expression amounts of adipocyte-specific proteins such as adipocyte fatty acid-binding protein 2 (aP2) and lipid metabolism enzymes such as fatty acid synthase (Fas) are increased. Furthermore, ADD1/SREBPs play an important role in lipid metabolism, but are also involved in the differentiation process. The expression of ADD1/SREBP1c in immature adipocytes is believed to contribute to the activation of PPARγ (Rosen E. D. et al., Annu. Rev. Cell Dev. Biol., 16, pp 145-171, 2000; Osborn T. F., J. Biol. Chem., 275, pp 32379-32382, 2000). Only adipocytes that have undergone the differentiation process synthesize fatty acids and store triglycerides. Therefore, current research trends are focused on the search for substances capable of inhibiting the metabolic process of adipogenic differentiation as a method for preventing or treating obesity and lipid-related metabolic diseases. In other words, attempts have been made to treat obesity through the regulation of adipocytes based on the mechanism of obesity, and these attempts have been intended to inhibit fat synthesis, reduce fat content by promoting lipolysis and oxidation, and reduce the number of adipocytes by inhibiting adipogenic differentiation, and transcription factors, proteins and adipokines, which are known to mediate or regulate these processes, are the targets of the development of new anti-obesity drugs. Actually, the peroxisome proliferator-activated receptor (PPAR) family, which is an adipogenic differentiation transcription factor, and leptin and adiponectin, which are adipocyte-secreted substances, have been the targets of many new drug development.
Current methods of treating obesity include dietetic therapy, exercise, and behavioral therapy, as well as methods of correcting daily habits, drug therapy, and surgical treatment. Obesity therapeutic agents are broadly classified into appetite suppressants, energy consumption promoters, and fat absorption inhibitors, such as Xenical™ (Roche Pharmaceuticals, Switzerland), Reductil™ (Abbott, USA), and Exolise™ (Atopharma, France), and most obesity drugs are appetite suppressants that suppress appetite by regulating the neurotransmitters associated with the hypothalamus. However, conventional therapeutic agents have been reported to have side effects such as heart disease, respiratory diseases, neurological diseases, and the like and low persistence of their efficacy. In addition, surgery for removing fat, gastroplasty or stomach band implantation for limiting the amount of food that can be digested by the body, and the like have been performed as obesity surgery methods, but therapeutic effects are not satisfactory compared to the side effects, surgery costs, and the like. For the fundamental treatment of obesity, there is a need for a new concept of obesity treatment based on the mechanisms capable of inhibiting the differentiation of pre-adipocytes into adipocytes.
Therefore, the applicants of the present invention completed the present invention. The present invention relates to a composition for treating obesity, which includes liquid type plasma, and the liquid type plasma of the present invention has a significant effect of inhibiting adipogenic differentiation and reducing intracellular lipogenesis and has an effect superior to that of a case in which a subject is directly treated with plasma, and thus it is anticipated that the composition of the present invention will be greatly utilized in preventing and treating obesity.